1. Field of the Invention
The present invention relates to an automatic analyzing method and apparatus for clinical examinations, suitable for performing remeasurement with respect to a sample from which abnormal data have been detected.
2.Description of the Related Art
In conventional biochemical clinical examinations, there exist factors that cause data abnormality. For example, data abnormality is caused when a certain component of serum taken from a patent exists at an extremely high concentration; when a patient takes a large dose of medicine for medical treatment; when blood is fatty because of corpulence and hence the serum becomes abnormally lipemic; and when regular use of vitamin C (ascorbic acid) results in high concentration of vitamin C (ascorbic acid), and reaction of a medicine with the vitamin C causes false positivity.
If a report to a doctor is made from such a clinical examination room without notation of these data abnormalities, the doctor may make a mistake in diagnosis of the patient. In the case where a normal patient tests abnormal as a result of such a situation, no serious problem occurs because the doctor carries out a close examination. But when an examination for an abnormal patient indicates a false normal result due to such an inaccurate test, however, a disease may be overlooked, resulting in a medical mistake. Further, this might cause a mistake in judgment of medical treatment. In a clinical examination room, check methods such as those hereafter described have been adopted in order to uncover such mistakes that occur as a result of examination to improve the reliability of report data.
In biochemical clinical examinations, examinations of several to more than thirty items are generally carried out for each patient.
(1) Checking low value and high value
An upper limit value and a lower limit value are set for each item contained in a serum sample, for example. If these values are exceeded for a sample, the sample is diluted with a physiological solution of sodium chloride or a buffer solution and a remeasurement is taken. A clinical examination engineer (hereafter abbreviated to engineer) performs a data judgment and report. An example of abnormality whereby the upper limit value or the lower limit value is exceeded is shown in FIG. 1 of U.S. Pat. No. 4,263,512. For a normal sample, the absorbance curve is located at a low level. If there is turbidity in the sample, the absorbance curve often rises to an abnormally high level.
(2) Checking change in absorbance
If high activity of an enzyme contained in a serum is measured, a co-enzyme contained in the reagent is consumed in a short time. Therefore, there is adopted a method such as rate analysis, whereby a change in absorbance (hereafter abbreviated to .DELTA.ABS) is detected at fixed time intervals and the activity of the enzyme is measured on the basis of these changes. If the measurement is performed after a predetermined time has elapsed since injection of a reagent, however, the change rate of absorbance is measured in some cases after reaction with the reagent has been finished, and the absorbance changes little. In this case, erroneous measurement results are obtained.
That is to say, .DELTA.ABS becomes large if the activity of the enzyme is high. If the activity of the enzyme is abnormally high, however, the substrate of the enzyme is rapidly consumed. When a predetermined time has elapsed, the reaction is substantially already finished. At this time, therefore, the measured value of .DELTA.ABS becomes very small.
In measurement of an enzyme, therefore, a check line of upper limit or lower limit with respect to the measured value of absorbance is set as ABS.multidot.LIMIT. If the reaction becomes rapid because of abnormally high activity of the enzyme, and hence the absorbance ABS exceeds the above described check line ABS.multidot.LIMIT, an alarm indicating a data abnormality is generated for the sample by an automatic analyzing apparatus.
In case of turbidity, red color and yellow color of serum are measured after addition of a buffer solution to serum, and a data abnormality in the enzyme item and in the lipid item shows up in serum information containing the influence from muddiness caused by fat of serum, the influence from bilirubin and the influence from hemolysis.
(3) Data cross-check between items
When the function of the liver, kidney and the like is examined in a clinical examination, examination is performed not for one item but for several items. For example, in the examination of the liver function, GOT, GPT, LDH, ALP, .gamma.-GTP and the like are examined. In case of patients having hepatitis, there is little possibility that only one item is abnormal and normal data are obtained in all other items. It is also unlikely that only one item is normal and all other items are abnormal. That is to say, a human body comprises various blood components that are mutually related and balanced. The engineer judges on the basis of these related data whether abnormalities in a certain item exist.
Some relations between these items are already known. Further, these relations are stored in a computer in the form of numerical formulas and used as a data check. Such a data crosscheck is disclosed in JJCLA (Japan Journal of Clinical Laboratory Automation), Japan Society for Clinical Laboratory Automation, Vol. 11, No. 5, 1986, pp. 58-62.
Conventionally, an engineer synthetically determines whether abnormalities exist by using these three kinds of representative data checking methods, and the engineer thus determines whether a readjustment should be made. Remeasurement may be made under the same condition as the condition of the first measurement or under a different condition. The engineer then compares the result of the remeasurement with the data obtained by the first measurement and judges which data should be reported to the doctor.
In the above described situations, three kinds of methods for determining whether data abnormalities exist are used separately. The engineer judges whether data are normal or not by watching these check results and determines whether a readjustment should be made or not. Problems of these methods will hereafter be described.
In the check of the upper limit value and the lower limit value described in (1), data of an item which should be originally abnormal become normal in some cases under the influence of another component contained in the serum. Because of the normality determination, the data of this item are not detected by this check. For checking these data abnormalities, turbidity and the like of the serum had to be checked in the check of absorbance change described in (2). Further, in the data cross-check between items described in (3), it was necessary to synthetically judge whether data were abnormal or not and whether reexamination was necessary or not on the basis of data of related items. Turbidity and hemolysis in serum, with resulting data abnormalities in some items, are difficult to determine in the data cross-check between items described in (3). It becomes possible, however, to detect the turbidity and hemolysis on the basis of absorbance level obtained after a reagent is added to serum by using the check of absorbance change rate described in (2).
At the present time, it is impossible to completely detect data abnormality by using, separately, any one of these three kinds of known methods. While watching results of these three kinds of check, the engineer makes a synthetic judgment and detects an abnormality. However, this synthetic judgment depends upon the experience of the engineer. Therefore, any judgment result varies with the engineer, and a person other than an expert may overlook a data abnormality. In a large hospital, the number of patients to be examined each day may be on the order of several hundred, and it is almost impossible for a person to carefully check data for all patients.
In general, samples judged to be abnormal are 5 to 10% of all samples. For an engineer to detect these few abnormal samples out of several hundred samples and request remeasurement of some items for each item is optimistic, and thus results in a problem.
In a system disclosed in JP-A-62-98262, an engineer performs a limit value check and a mutual check between items on the basis of various data obtained from the automatic analyzing apparatus, and reexamination is performed when an abnormal sample is found out.
On the other hand, in an automatic chemical analyzing apparatus disclosed in JP-A-61-262662, a value measured by the automatic chemical analyzing apparatus is compared with a reference value, and if the measured value exceeds the reference value, that sample is automatically transferred again to an examination station for reexamination of the sample.